Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis.
Humans; *Apoptosis; *Apoptosis; *ERK1/2; *Nrf2; *Osteoarthritis; *Redox; Oxidative Stress; Osteoarthritis/*metabolism; NF-E2-Related Factor 2/genetics/*metabolism; Up-Regulation; MAP Kinase Signaling System; Chondrocytes/*physiology; Caspases/metabolism; Cells; Cultured; 70-kDa/metabolism; Ribosomal Protein S6 Kinases; Carboxylic Ester Hydrolases/metabolism; ets-Domain Protein Elk-1/metabolism; Interleukin-1beta/immunology; 90-kDa/metabolism
Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1beta stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient. Human chondrocytes treated with IL-1beta resulted in robust Nrf2/ARE reporter activity, which was inhibited by pretreatment with antioxidants indicating that Nrf2 activity was due to IL-1beta-induced ROS generation. Ectopic expression of Nrf2 significantly suppressed the IL-1beta-induced generation of ROS while Nrf2 knockdown significantly increased the basal as well as
Khan Nazir M; Ahmad Imran; Haqqi Tariq M
Free radical biology & medicine
2018
2018-02
<a href="http://doi.org/10.1016/j.freeradbiomed.2018.01.013" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2018.01.013</a>
Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-kappaB and Nrf2 Signaling Pathways.
Female; Animals; Anti-Inflammatory Agents/*pharmacology; Rats; Gene Expression Regulation; Signal Transduction; Apoptosis/drug effects; anti-inflammatory effects; Anticarcinogenic Agents/pharmacology; breast tumor; COX-2; Cyclooxygenase 2/genetics/metabolism; DMBA; HSP90; HSP90 Heat-Shock Proteins/genetics/metabolism; I-kappa B Kinase/genetics/metabolism; NF-E2-Related Factor 2/genetics/*metabolism; NF-kappa B/genetics/*metabolism; NF-kappaB; Nrf2; Plant Preparations/*pharmacology; Punica granatum; Punicaceae/*chemistry; Pomegranate; Chemoprevention; Dose-Response Relationship; Drug; Neoplastic; Mammary Neoplasms; 10-Dimethyl-1; 9; Neoplastic/drug effects; Cell Transformation; 2-benzanthracene/toxicity; Experimental/*prevention & control; Animal Studies; Breast Neoplasms; Inflammation Mediators; Physical Education and Training; Neoplasms – Prevention and Control
Pomegranate (Punica granatum L.), a nutrient-rich unique fruit, has been used for centuries for the prevention and treatment of various inflammation-driven diseases. Based on our previous study, a characterized pomegranate emulsion (PE) exhibited a striking inhibition of dimethylbenz(a)anthracene (DMBA)-initiated rat mammary tumorigenesis via antiproliferative and apoptosis-inducing mechanisms. The objective of the present work is to investigate the anti-inflammatory mechanism of action of PE during DMBA rat mammary carcinogenesis by evaluating the expression of cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-kappaB (NF-kappaB) and nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2-5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-kappaB, inhibitory kappaBalpha (IkappaBalpha) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IkappaBalpha, hindered the translocation of
Mandal Animesh; Bhatia Deepak; Bishayee Anupam
Nutrients
2017
2017-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3390/nu9050436" target="_blank" rel="noreferrer noopener">10.3390/nu9050436</a>
Black currant anthocyanins abrogate oxidative stress through Nrf2- mediated antioxidant mechanisms in a rat model of hepatocellular carcinoma.
Male; Animals; Rats; Diet; Signal Transduction; NF-E2-Related Factor 2/genetics/*metabolism; *Phytotherapy; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Alkylating Agents/toxicity; Anthocyanins/*therapeutic use; Antioxidants/therapeutic use; Diethylnitrosamine/toxicity; Glutathione Transferase; Immunoenzyme Techniques; Lipid Peroxidation/drug effects; Nitric Oxide Synthase Type II/genetics/metabolism; Oxidative Stress/*drug effects; Ribes/*chemistry; Tyrosine/analogs & derivatives/metabolism; Carcinoma; Sprague-Dawley; Blotting; Western; RNA; Liver Neoplasms; Messenger/genetics; Experimental/chemically induced/metabolism/*prevention & control; Hepatocellular/chemically induced/metabolism/*prevention & control
Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost \textgreater 1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off potential cancer risks and mortality. A major predisposing condition, pertinent to the development and progression of HCC is oxidative stress. We previously reported a striking chemopreventive effect of anthocyanin-rich black currant skin extract (BCSE) against diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats. The current study aims to elucidate the underlying antioxidant mechanisms of black currant anthocyanins implicated in the previously observed chemopreventive effects against experimental hepatocarcinogenesis. Dietary BCSE (100 and 500 mg/kg) administered four weeks before and 18 weeks after DENA challenge decreased abnormal lipid peroxidation, protein oxidation, and expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in a dose-responsive fashion. Mechanistic studies revealed that BCSE upregulated the gene expression of a number of hepatic antioxidant and carcinogen detoxifying enzymes, such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes, in DENA-initiated animals. Protein and mRNA expressions of nuclear factor E2-related factor 2 (Nrf2) were substantially elevated with BCSE treatment, providing a direct evidence of a coordinated activation of the Nrf2-regulated antioxidant pathway, which led to the upregulation of a variety of housekeeping genes. The results of our study provide substantial evidence that black currant bioactive anthocyanins exert chemopreventive actions against DENA-inflicted hepatocarcinogenesis by attenuating oxidative stress through activation of Nrf2 signaling pathway.
Thoppil Roslin J; Bhatia Deepak; Barnes Kendra F; Haznagy-Radnai Erzsebet; Hohmann Judit; Darvesh Altaf S; Bishayee Anupam
Current cancer drug targets
2012
2012-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2174/156800912803987968" target="_blank" rel="noreferrer noopener">10.2174/156800912803987968</a>